These studies are directed toward biochemical probing of the structure of plasma low density lipoproteins with the purpose of understanding the structure-function relationships of the apoprotein, apo-beta. The work has proceeded along two lines. On the one hand, we are pursuing our studies on the proteolytic cleavage of native LDL and on the isolation of the polypeptides liberated by brief tryptic digestion of this lipoprotein. Our objective for the forthcoming year is the purification of a series of large polypeptides liberated by tryptic cleavage of apo-Beta. As soon as purification is achieved, it is our plan to utilize these polypeptides in studying the interaction of apo-beta with the fibroblast receptor for LDL; to prepare peptide-specific antibodies which can be used in initiating studies of the organization of apo-beta within native LDL, and to develop a collaborative program for the purpose of sequencing these large polypeptides. The other aspect of our research concerns the study of delipidated apo-beta and its interaction with the LDL cellular receptor. Within the past year we have succeeded in solubilizing fully delipidated apo-beta and have recently demonstrated that apo-beta is recognized by the fibroblast receptor and that this binding meets the criteria for specific high affinity interaction between the receptor and the protein. We now plan to explore the binding of peptides from apo-beta to the fibroblast receptor with the hope of being able to define the peptide binding domain of apo-beta which is recognized by the receptor. BIBLIOGRAPHIC REFERENCES: Fisher, W.R., and Shireman, R.B. "Demonstration of the specificity for binding by the low density lipoprotein fibroblast receptor for apolipoprotein-beta." Fed. Proc., 1977, in press. Fisher, W.R., and Truitt, D.H. "The common hyperlipoproteinemias: An understanding of disease mechanisms and their control." Ann. Int. Med. 85(4): 496-508, 1976.